B7-H1 antibodies lose antitumor activity due to activation of p38 MAPK that leads to apoptosis of tumor-reactive CD8⁺ T cells.

ABSTRACT: B7-H1 (aka PD-L1) blocking antibodies have been used in treatment of human cancers through blocking B7-H1 expressed by tumor cells; however, their impact on B7-H1 expressing tumor-reactive CD8⁺ T cells is still unknown. Here, we report that tumor-reactive CD8⁺ T cells expressing B7-H1 are functional effector cells. In contrast to normal B7-H1 blocking antibody, B7-H1 antibodies capable of activating p38 MAPK lose their antitumor activity by deleting B7-H1⁺ tumor-reactive CD8⁺ T cells via p38 MAPK pathway. B7-H1 deficiency or engagement with certain antibody results in more activation of p38 MAPK that leads to T cell apoptosis. DNA-PKcs is a new intracellular partner of B7-H1 in the cytoplasm of activated CD8⁺ T cells. B7-H1 suppresses

SUBMITTER: Liu X 

PROVIDER: S-EPMC5099859 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature